Our laboratory is studying ways to generate, expand, and therapeutically administer lymphoid cells with antitumor effects to tumor-bearing animals. We are currently examining in situ tumor immunity and its exploitation using interleukin-2 to culture tumor- infiltrating lymphocytes (TIL). Our approach is to first optimize in situ immunity through studies of tumor immunogenicity, host response to transplanted murine tumors and the effects of exogenous lymphokine therapy. Secondly, techniques for the in vitro culture of TILs maintaining maximal therapeutic efficacy will investigated. These techniques include manipulations of growth factors, feeder cells, and tumor antigen. Thirdly, investigations on the in vivo traffic of transferred cells will continue with the objective of clarifying and enhancing the conditions which cause localization of cells to tumor sites. Lastly, in vitro parameters which can predict therapeutic efficacy of TILs are being sought so that rational treatment strategies can be designed based on these predictors of response. A separate project which is on-going is to investigate the mediators of toxicity during interleukin-2 therapy. Studies will include mainly investigation of leukotriene levels and inhibitors of the formation of leukotrienes. In addition, cell transfer experiments investigating the cellular mediators of toxicity are on-going.